This disclosure relates to methods for the manufacture of 2-aryl-3,3-bis(4-hydroxyaryl)phthalimidines.
Production of 2-phenyl-3,3-bis(4-hydroxyphenyl)phthalimidine (also known as N-phenyl phenolphthalein bisphenol (PPPBP) or 3,3-bis(4-hydroxyphenyl)-2-phenylisoindolin-1-one)) can be synthesized in two-step batch processes. The first step is making phenolphthalein (PP), by reacting phthalic anhydride with phenol in the presence of zinc chloride and chlorosulphonic acid as a co-catalyst at elevated temperature in a batch reactor, as described, for example, in U.S. Pat. No. 2,522,939. The purification and isolation of phenolphthalein is also performed batch-wise, for example as described in U.S. Patent Publication 2008/0177091, where the reaction mass is transferred to two or more additional vessels, filtered (sometimes in separate batches) and isolated. The second synthesis step is the reaction of the PP with aniline in the presence of an acid, followed by isolation to provide a crude product, as described, for example, in U.S. Pat. No. 8,809,486. The solid crude PPPBP is obtained after filtration and washing with water. Purification of crude PPPBP is usually also conducted in a batch process, for example as described in U.S. Pat. Nos. 7,135,577, 7,563,817, and 7,884,220. The total process can involve eight, ten, or more manual interventions.
There accordingly remains a need for improved methods for the manufacture of 2-phenyl-3,3-bis(4-hydroxyphenyl)phthalimidine, and in particular PPPBP.